P1269: PRIMARY GRAFT FAILURE INCIDENCE, RISK FACTORS, AND OUTCOMES IN PATIENTS UNDERGOING NON-MYELOABLATIVE ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION USING POST-TRANSPLANT CYCLOPHOSPHAMIDE
Authors: Jonaphine Mata, Natalie S. Rosen, Marianna Zahurak, Richard Jones, Alex Ambinder
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Primary graft failure (PGF) is a major complication of alloHCT that results in significant morbidity and mortality. Factors previously associated with PGF include HLA disparity, ABO mismatching in the donor/recipient pair, reduced-intensity conditioning, underlying diagnosis, graft source, cell dose, graft manipulation, and viral reactivation (Olsson et al., Novitzky-Basso et al., Chen et al., Glotzbecker et al.). Post-transplant cyclophosphamide (PTC-y)-based graft versus host disease (GVHD) prophylaxis has recently emerged as the standard in the field, but few studies have investigated the characteristics of PGF in the setting of PTCy-based GVHD prophylaxis (Hickey et al.) Aims: In this study, we aim to describe the incidence, clinical features, risk factors and relapse-free and overall survival of patients who experienced PGF after non-myeloablative (NMA) alloBMT with the use of PTCy-based GVHD prophylaxis Methods: This is a retrospective, single institution study of 1028 patients 18 and older who underwent first, NMA alloBMT with PTCy-based GVHD prophylaxis between 07/01/2016 and 06/30/2021 who were selected for inclusion. We defined PGF as patients who did not achieve an ANC of 500 cells/m3 by day 30 and is the primary analysis set (Kharfan-Dabaja et al.). We defined patients with delayed engraftment (DE) as those who achieve an ANC of 500 cells/m3 after day 30 with full donor chimerism, differentiating them from those with PGF who never achieved count recovery or who achieved count recovery with mixed or recipient chimerism. A second analysis set reports findings on patients with DE. We performed a multivariate analysis assessing the significance of multiple factors between patients who had PGF and patients with normal engraftment. Overall survival (OS) and relapse-free survival (RFS) are reported using the Kaplan-Meier and reverse Kaplan-Meier methods. The cumulative incidence of relapse and non-relapse mortality (NRM) outcomes were assessed with the proportional subdistribution hazard regression model for competing risks. Results: Of the 1028 alloBMT recipients, 41 (3.9%) were identified with PGF. Out of the 41 patients, 29 experienced DE in our second analysis set. The remainder died in aplasia (7) or achieved count recovery with mixed or recipient chimerism (5). In our multivariate analysis, patient age > 60 (OR=2.089, p=0.0286), donor age > 55 (OR=7.921, p=0.0025) and patients with the diagnoses of Myelodysplastic Syndrome or Myeloproliferative Neoplasms (MDS/MPN) (OR=2.533, p=0.0058) were significantly associated with the development of PGF. Neither donor relationship or HLA matching were associated with PGF. The median OS for patients experiencing PGF after NMA alloBMT with PTCy was 5.91 months and the RFS was 5.72 months. The median OS for patients with DE was 7.03 months and the RFS was 7.03 months. The probability of NRM was 57% at 36 months, compared to 18% for mortality due to relapse (Figure 1). Whereas for patients with DE, the probability of NRM was 56%, compared to 14% for mortality due to relapse. Summary/Conclusion: PGF is an uncommon complication in those undergoing NMA alloBMT with PTCy and is not increased in recipient-donor pairs with HLA mismatch. Our study highlights the significant morbidity and mortality associated with these phenomena and identifies older recipient age, older donor age, and an underlying diagnosis of MDS/MPN as risk factors for PGF. In an era where most patients have multiple potential donors, these data highlight the importance of young donor age in the selection process. Furthermore, older recipients and those with MDS/MPN should be counseled on the increased risk of PGF and the poor outcomes associated with it.Keywords: allo BMT, Allogeneic stem cell transplant, Bone marrow transplant, Allogeneic bone marrow transplant